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Translation of abstract (English)

The activating transcription factor 1 (ATF1), the cAMP response element binding protein (CREB) and the cAMP response element modulatory protein (CREM), a subfamily of the basic leucine zipper transcription factors, share high sequence homology and mediate the transcriptional response to various extracellular signals, including peptide hormones, growth factors, neurotransmitters and Ca2+. Activation of the CREB/CREM/ATF1 proteins is mediated via different signaling pathways which converge to phosphorylate a distinct serine residue. ATF1, CREB and CREM activate gene expression by binding as homo- or heterodimers to the cAMP response element (CRE) in regulatory regions of target genes. To investigate the in vivo function the corresponding genes were inactivated by homologous recombination. Mice lacking the CREM gene exhibit an arrest in spermatogenesis. In contrast to CREB deficient mice, which suffer from perinatal lethylity due to atelectasis of the lung, mice lacking ATF1 do not exhibit any discernible phenotypic abnormalities. ATF1 and CREB, but not CREM, are strongly coexpressed during early mouse development. To identify the role of both proteins during early development and to circumvent possible compensatory effects, we therefore generated mice deficient for both, ATF1 and CREB. Complete inactivation of both proteins, ATF1 and CREB, results in developmental arrest and embryonic death before implantation. Embryos with only one functional ATF1 allele, in the absence of CREB, develop further but display severe structural defects and die around E9.5. Therefore, ATF1 and CREB proteins, play a crucial role during early mouse development. They can compensate for each other´s function, although they are not equivalent implying that the influence of each factor differs during early development.